Title (en)

Enhancement of expression of a single-stranded, heterologous nucleotide sequence from recombinant viral vectors by designing the sequence such that it forms intrastrand base pairs

Title (de)

Erweiterte Expression einer einstämmigen, heterologen Nukleotidsequenz von rekombinanten viralen Vektoren durch Modellierung der Sequenz mit stammübergreifenden Basispaaren

Title (fr)

Améliorations de l'expression d'une séquence de nucléotides hétérologues à brin unique à partir de vecteurs viraux recombinants par la désignation de la séquence de manière à ce qu'elle forme des paires de bases intrabrins

Publication

EP 1916258 B1 20140423 (EN)

Application

EP 07022775 A 20000808

Priority

• EP 00953892 A 20000808
• US 16008099 P 19990809

Abstract (en)

[origin: EP1916258A2] The present invention provides a recombinant adeno-associated virus (rAAV) virus preparation, which rAAV virus preparation is essentially free of other viruses, comprising an rAAV vector, wherein the rAAV vector comprises a single-stranded heterologous nucleotide sequence comprising a coding region which forms intrastrand base pairs such that expression of the coding region of the heterologous sequence is enhanced relative to an rAAV vector that lacks sufficient intrastrand base pairing to enhance said expression, wherein the rAAV vector comprises one or more inverted terminal repeat (ITR) sequences flanking said heterologous sequence, wherein the rAAV vector is less than 2.5 kilobases in length, wherein the total amount of unique sequence present in the heterologous sequence is about one-half of the heterologous sequence and wherein the heterologous sequence forms intrastrand base pairs along most or all of its length, for use in a method of treatment of the human or animal body by therapy.

IPC 8 full level

C12N 5/10 (2006.01); C12N 7/01 (2006.01); C12N 15/86 (2006.01); C12N 15/864 (2006.01)

CPC (source: EP)

C12N 15/86 (2013.01); C12N 2750/14143 (2013.01)

Citation (examination)

• FERRARI F K ET AL: "New developments in the generation of Ad-free, high-titer rAAV gene therapy vectors", NATURE MEDICINE, NATURE PUBLISHING GROUP, NEW YORK, NY, US, vol. 3, no. 11, 1 November 1997 (1997-11-01), pages 1295 - 1297, XP002098257, ISSN: 1078-8956, DOI: 10.1038/NM1197-1295
• XIAO X ET AL: "Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus.", JOURNAL OF VIROLOGY MAR 1998, vol. 72, no. 3, March 1998 (1998-03-01), pages 2224 - 2232, ISSN: 0022-538X
• MCCOWN T J ET AL: "Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector.", BRAIN RESEARCH 25 MAR 1996, vol. 713, no. 1-2, 25 March 1996 (1996-03-25), pages 99 - 107, ISSN: 0006-8993
• GRIMM DIRK ET AL: "Adeno-associated virus vectors for short hairpin RNA expression.", METHODS IN ENZYMOLOGY 2005, vol. 392, 2005, pages 381 - 405, ISSN: 0076-6879

Citation (opposition)

Opponent : Genzyme Corporation

• WO 9911764 A2 19990311 - TARGETED GENETICS CORP [US], et al
• WO 9732018 A2 19970904 - IMMUSOL INC [US], et al
• WO 9947691 A1 19990923 - UNIV PENNSYLVANIA [US], et al
• WO 9717458 A1 19970515 - AVIGEN INC [US]
• WO 9528493 A1 19951026 - UNIV ROCKEFELLER [US], et al
• WO 9513392 A1 19950518 - OHIO MED COLLEGE [US], et al
• WO 9528948 A1 19951102 - UNIV TEXAS [US]
• HERMENS: "Viral vectors; towards application in neuroregeneration research/WTJMC Hermens-Utrecht", THESIS, 1997, pages 149 - 164, ISBN: 90-9010642-1
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• DONG ET AL.: "quantitative analysis of the packaging capacity of recombinant adeno associated virus", HUMAN GENE THERAPY, vol. 7, 1996, pages 2101 - 2112, XP000985472
• HÖRSTER ET AL.: "recombinant aav-2 harbouring gfp antisense/ribozyme fusion sequences monitor transduction, gene expression and show anti-HIV-1 efficacy", GENE THERAPY, vol. 6, July 1999 (1999-07-01), pages 1231 - 1238, XP055305298
• HOMANN ET AL.: "incorporation of the catalytic domain of a hammerhead ribozyme into antisense RNA enhances its antisense RNA enhances its inhibitory effect on the replication of human immunodeficiency virus type 1", NUCLEIC ACIDS RESEARCH, vol. 21, 1993, pages 2809 - 2814, XP002051227
• PHILLIPS ET AL.: "prolonged reduction of high blood pressure with an in vivo nonpathgenic adeno-associated viral vector delivery of AT1-R mRNA antisense", HYPERTENSION, vol. 29, 1997, pages 374 - 380, XP055305299
• WELCH ET AL.: "ribozyme gene therapy for hepatitis c virus infection", CLINICAL AND DIAGNOSTIC VIROLOGY, vol. 10, 1998, pages 163 - 171, XP055305300
• SU ET AL.: "Selective Killing of AFP-Positive Hepatocellular Carcinoma Cells by Adeno-Associated Virus Transfer of the Herpes Simplex Virus Thymidine Kinase Gene", HUMAN GENE THERAPY, vol. 7, 1996, pages 463 - 470, XP055305301
• ZOLUTUKHIN: "a humanized green fluorescent protein cDNA adapted for high level expression in mammalian cells", J VIROL, vol. 70, 1996, pages 4646 - 4654, XP002047302
• MAMOUNAS ET AL.: "increased titer of recombinant aav vectors by gene transfer with adenovirus coupled to DNA-polylysine complexes", GENE THERAPY, vol. 2, 1995, pages 429 - 432, XP055305302
• FERRARI ET AL.: "new developments in the generation of ad-free high titer rAAV gene therapy vectors", NATURE MEDICINE, vol. 3, no. 11, 1997, pages 1295 - 1297, XP002098257
• FERRARI ET AL.: "second-strand synthesis is a rate limiting step for efficient transduction by recombinant adeno-associated virus vectors", JOURNAL OF VIROLOGY, vol. 70, no. 5, 1996, pages 3227 - 3234, XP002003300
• XIAO ET AL.: "production of high-titer recombinant adeno-associated virus vectors in the absence", JOURNAL OF VIROLOGY, vol. 72, no. 3, 1998, pages 2224 - 2232, XP002924402
• FISHER ET AL.: "transduction with recombinant adeno-associated virus for gene therapy is limited by leading strand synthesis", JOURNAL OF VIROLOGY, 1996, pages 520 - 532, XP000570468
• CURRICULUM VITAE OF DR WIM HERMENS
• DECLARATION BY DR WIM HERMENS
• CURRICULUM VITAE OF PROF DR JOOST VERHAAGEN
• DECLARATION BY PROF DR JOOST VERHAAGEN
• MUZYCZKA: "use of adeno associated virus as a general transduction vector for mammalian cells", CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY, vol. 158, 1992, pages 97 - 129, XP002927890
• BARRIE J. CARTER;: "Variant and Defective Interfering Parvoviruses", THE PARVOVIRUSES;, 1984, New York and London, XP055305304
• JEFFREY BARTLETT ET AL.: "Genetics and Biology of Adeno-Associated Virus", VIRAL VECTORS - GENE THERAPY AND NEUROSCIENCE APPLICATIONS;, 1995, XP055305306
• MICHAEL KAPLITT ET AL.: "Transfer and Expression of Potentially Therapeutic Genes into the Mammalian Central Nervous System in Vivo Using Adeno-Associated Viral Vectors", VIRAL VECTORS - GENE THERAPY AND NEUROSCIENCE APPLICATIONS;, 1995, XP055305307
• "Adeno-Associated Virus (AAV) Virus 2 mediated transduction and erythroid lienage specific expression in human hematopoietic progenitor cells", CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY, vol. 218, 1996, pages 93 - 117, XP055305311
• "Adeno-Associated Virus (AAV) Vectors in Gene Therapy;", CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY, vol. 218, 1996, pages 119 - 144
• "Adeno-Associated Virus (AAV) Vectors in Gene Therapy;", CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY, vol. 218, 1996, pages 145 - 173
• "Adeno-Associated Virus (AAV) Vectors in Gene Therapy;", CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY, vol. 218, 1996, pages 1 - 23
• CALCULATION OF SIZE OF RAAV VECTORS DISCLOSED IN D7

Designated contracting state (EPC)

AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

DOCDB simple family (publication)

EP 1916258 A2 20080430; EP 1916258 A3 20090408; EP 1916258 B1 20140423

DOCDB simple family (application)

EP 07022775 A 20000808